1. Field of the Invention
The present invention relates generally to the fields of molecular immunology and therapies for the Acquired Immune Deficiency Syndrome (AIDS). More specifically, the present invention relates to novel immunotoxins for the treatment of AIDS.
2. Description of the Related Art
With more than six million people worldwide infected with the HIV virus, effective therapies for this disease are desperately needed. While research on developing vaccines is being actively pursued, the nature of the virus makes this an exceptionally difficult, long term task. Moreover, treatment of current AIDS cases is severely limited. Only one drug, azidothymidine (AZT) is currently registered for the full use in the U.S. There are however problems with strains of HIV resistant to AZT developing. As mutant forms of the virus appear, the degree of resistance increases. The prevailing theory on virus resistance was that the virus mutated at such rapid rates that more resistant forms appeared rather quickly. Recent studies, however, suggest that this resistance is not a result of hypermutability, but possibly a consequence of the high level of replication of the virus.
Regardless of the mechanisms of resistance, AZT is not effective for a long period of time. This treatment is also extremely expensive and has several accompanying side effects such as nausea, seizures, liver function abnormalities, and bone marrow suppression. Other chemical variants of AZT, such as DDC and DDI, show promise in clinical trials but are, however, of limited effectiveness. Although a number of other drugs and treatment regimes are being investigated, there is clearly a pressing need for additional drugs and new approaches to treating this disease.
Experimental immunotherapy approaches to AIDS have shown some promise, but most exhibit very wide variability of effectiveness, primarily because of the highly variable nature of the target molecules. These target molecules, such as the HIV envelope proteins, vary from strain to strain and from patient to patient.
Immunotoxin therapy has, however, proven very effective against several other diseases when there is an absolutely specific target for the antibody portion of the antibody-toxin conjugates. For example, the Pseudomonas exotoxin was coupled to a monoclonal antibody targeted against ovarian cancer tumors. It effectively inhibited the growth of human ovarian cancer cells in a mouse model (Willingham, M. C., et al., 1987). What is needed for AIDS immunotherapy is a highly specific and unvarying target.
The HIV enzyme reverse transcriptase (RT) is of absolutely critical importance for viral replication. The enzyme plays an essential role in catalyzing the formation of a DNA copy of the viral genetic material (RNA). The DNA is then used either for generating more copies of the virus immediately or for integration into the patient's genome, for later expression of the disease. This critical role of reverse transcriptase is likely the reason for its highly conserved structure. Moreover, it was recently shown that, when cells are infected with HIV, copies of the reverse transcriptase (or portions thereof) are attached to the exterior cell surface. The cell surface expression of the reverse transcriptase is markedly greater than that for even the viral envelope proteins.
The prior art is deficient in the lack of effective means of therapeutically treating the acquired immune deficiency syndrome. The present invention fulfills this longstanding need and desire in the art.